Document Detail

Endomysial fibrosis in Duchenne muscular dystrophy: a marker of poor outcome associated with macrophage alternative activation.
MedLine Citation:
PMID:  19535995     Owner:  NLM     Status:  MEDLINE    
There is considerable interindividual variability in motor function among patients with Duchenne muscular dystrophy (DMD); moreover, pathogenetic mechanisms of motor dysfunction in DMD are not understood. Using multiparametric analysis, we correlated initial histologic alterations in quadriceps muscle biopsies from 25 steroid therapy-free patients with DMD with 13 relevant clinical features assessed by a single clinical team during a long-term period (mean, >10 years). There was no residual muscle dystrophin by immunohistochemistry and Western blot analysis in the biopsies. Myofiber size, hypercontracted fibers, necrotic/basophilic fibers, endomysial and perimysial fibrosis, and fatty degeneration were assessed by morphometry. Endomysial fibrosis was the only myopathologic parameter that significantly correlated with poor motor outcome as assessed by quadriceps muscle strength, manual muscle testing of upper and lower limbs at 10 years, and age at ambulation loss (all p<0.002). Motor outcome and fibrosis did not correlate with genotype. Myofibers exhibited oxidative stress-induced protein alterations and became separated from capillaries by fibrosis that was associated with both increase of CD206+ alternatively activated macrophages and a relative decrease of CD56+ satellite cells (both p<0.0001). This study provides a strong rationale for antifibrotic therapeutic strategies in DMD and supports the view that alternatively activated macrophages that are known to inhibit myogenesis while promoting cellular collagen production play a key role in myofibrosis.
Isabelle Desguerre; Michelle Mayer; France Leturcq; Jacques-Patrick Barbet; Romain K Gherardi; Christo Christov
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of neuropathology and experimental neurology     Volume:  68     ISSN:  0022-3069     ISO Abbreviation:  J. Neuropathol. Exp. Neurol.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-06-30     Completed Date:  2009-08-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985192R     Medline TA:  J Neuropathol Exp Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  762-73     Citation Subset:  IM    
AP-HP, Necker - Enfants Malades Hospital, Neuropediatry Unit, Paris, France.
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MeSH Terms
Antigens, CD56 / metabolism
Capillaries / pathology
Child, Preschool
Dystrophin / genetics
Fibrosis / pathology
Follow-Up Studies
Lectins, C-Type / metabolism
Macrophage Activation
Macrophages / metabolism,  pathology
Mannose-Binding Lectins / metabolism
Motor Activity / physiology
Muscle Strength
Muscle, Skeletal / blood supply,  pathology*
Muscular Dystrophy, Duchenne / complications,  diagnosis*,  pathology*,  physiopathology
Myofibrils / pathology
Oxidative Stress
Receptors, Cell Surface / metabolism
Satellite Cells, Skeletal Muscle / metabolism,  pathology
Reg. No./Substance:
0/Antigens, CD56; 0/Dystrophin; 0/Lectins, C-Type; 0/Mannose-Binding Lectins; 0/Receptors, Cell Surface; 0/mannose receptor

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